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Immunoglobulin G glycosylation changes in diseases and aging

Background: Immunoglobulin G (IgG) is one of the key players in various immune response pathways, involved in the protection against invading pathogens but also inducing inflammation and tissue destruction in autoimmune disorders and other diseases with an inflammatory component. Each IgG molecule contains two biantennary N-glycans covalently attached to the conserved N-glycosylation sites at Asn-297 on each of its heavy chains. IgG glycans are of key importance for structural stabilization of the Fc region as well as for the IgG effector functions, affecting IgG binding affinity for FcγRs and other receptors, thus participating in the fine-tuning of the molecule’s biological activity. Polyclonal IgG glycosylation varies markedly in different physiological and pathological states (age ; gender, pregnancy, menopause ; infectious, inflammatory and autoimmune diseases, cancers). However, changes observed in different diseases often show similar patterns (e.g. decreased galactosylation and sialylation), which diminishes specific biomarker potential of the IgG glycome when it comes to individual diseases. Aim: The aim of this study was to compare IgG glycome in all large studies performed in our lab with the purpose of identifying possible shared and disease-specific biomarkers in the IgG glycome. Materials and methods: We compiled the data from 19 different cohorts comprising over 15.000 subjects and examined the changes of IgG glycome with age and in people suffering from different diseases: systemic lupus erythematosus, ulcerous colitis, Crohn’s disease, rheumatoid arthritis, Hashimoto’s thyroiditis, allergic sensitization, type 2 diabetes and colorectal carcinoma. Since the IgG glycomics data have been obtained using different analytical methods: hydrophilic interaction ultraperformance liquid chromatography (HILIC UPLC) and liquid chromatography mass spectrometry (LC MS), the analysis was performed on major derived traits: agalactosylation, digalactosylation, sialylation, fucosylation and the presence of bisecting N acetylglucosamine. Results: The changes in IgG glycome composition in many different diseases resemble the changes that occur with aging: most notably, a decrease in the abundance of galactosylated and sialylated structures was observed, reflecting the loss of immunosuppressive potential of IgG. Systemic lupus erythematosus and type 2 diabetes patients, in addition, display an increase in the abundance of structures with bisecting N acetylglucosamine, also seen in aging. Conclusion: IgG glycome seems to be an indicator of common processes underlying various diseases and aging. The fact that the alterations in IgG glycosylation patterns that are known to significantly affect IgG’s inflammatory capacity are similar across different diseases and aging points to IgG glycome as one of the mechanisms contributing to the aging process and disease development through modulation of inflammation.

IgG glycome ; disease ; aging ; differential glycosylation ; biomarker

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